A disease state, caused or effected by a pneumococcal infection, is often difficult to diagnose.
Pneumonia is an acute, occasionally chronic, infection of the lower respiratory tract caused by a variety of pathogens including bacteria, viruses, fungi and parasites1,2. A variety of non-infectious processes such as congestive heart failure, pulmonary infarction, vasculitis, and drug reactions can mimic pneumonia3. Despite progress in the development of antibiotics, diagnostic imaging, and critical care medicine, pneumonia remains the leading cause of death from infection in North America mainly because of the difficulty in promptly identifying the etiologic agent4,5. In practice, leas than 20% of patients admitted to hospital with pneumonia obtain an etiological diagnosis4,6.
Streptococcus pneumoniae, the major causative pathogen of pneumonia7, is a transient commensal organism of the throat and upper respiratory tract8 in ˜40% of the population. However, S. pneumoniae frequently becomes virulent, especially for those at the extremes of age, immunocompromised individuals, those with chronic diseases, and tobacco smokers6. Each year, millions of people in the United States are infected resulting in 500,000 hospitalizations9. Indeed, invasive S. pneumoniae is a leading cause of death worldwide, with a mortality rate of up to 25%10.
Currently, diagnosis of a disease state effected by or caused by an infectious lung disease, such as pneumococcal pneumonia, is made by positive blood or sputum culture (pleural fluid or material obtained by bronchoalveolar lavage (BAL) may also be cultured) in the presence of a compatible clinical picture. Blood and sputum cultures yield S. pneumoniae in 6-10% and 11% of patients respectively11. Moreover, results are rarely available within 36 hours, and a positive sputum culture for S. pneumoniae only indicates that this pathogen is possible or at best a probable cause of pneumonia9. To combat lengthy diagnostic times, other tests have been developed such as the NOW test (Binax Inc.) which detects cell wall polysaccharide of S. pneumoniae in urine. However, this test is positive for only about 80-90% of bacteremic patients12. Since no gold standard test exists for those disposed in a disease state effected or caused by an infectious lung disease, such as non-bacteremic pneumococcal pneumonia, we do not know whether this test has value. Furthermore, a 65% false positive rate is seen with this test in children who carry this microorganism asymptomatically in their nasopharynx12.
An ideal diagnostic tool for the disease state effected or caused by an infectious lung disease such as S. pneumoniae infection, would be one that is non-invasive, requires a minimal amount sample not contaminated by carriage of the organism from the site at which it was obtained, can be done quickly with high sensitivity and specificity, is technically simple to carry out, and ideally inexpensive.
Metabolomics is an emerging science dedicated to the global study of metabolites; their composition, interactions, dynamics, and responses to disease or environmental changes in cells, tissues and biofluids. While the idea of using metabolomics for diagnostic purposes is not new, technology has changed significantly and sufficiently to allow the simultaneous measurement of literally hundreds of metabolites at once. A number of metabolomics studies have reported differences between disease and healthy states and these have been previously reviewed13-15.